Medicine and Health Sciences Commons^™

Directional Secretory Response Of Double Stranded Rna-Induced Thymic Stromal Lymphopoetin (Tslp) And Ccl11/Eotaxin-1 In Human Asthmatic Airways, Gustavo Nino, Shehlanoor Huseni, Geovanny F. Perez, Krishna Pancham, Humaira Mubeen, Aleeza Abeesi, Justin Wang, Stephen Eng, Anamaris M. Colberg-Poley, Mary C. Rose

Pediatrics Faculty Publications

Background

Thymic stromal lymphoproetin (TSLP) is a cytokine secreted by the airway epithelium in response to respiratory viruses and it is known to promote allergic Th2 responses in asthma. This study investigated whether virally-induced secretion of TSLP is directional in nature (apical vs. basolateral) and/or if there are TSLP-mediated effects occurring at both sides of the bronchial epithelial barrier in the asthmatic state.

Methods

Primary human bronchial epithelial cells (HBEC) from control (n = 3) and asthmatic (n = 3) donors were differentiated into polarized respiratory tract epithelium under air-liquid interface (ALI) conditions and treated apically with dsRNA (viral surrogate) …

Integrative Therapy Use For Management Of Side Effects And Toxicities Experienced By Pediatric Oncology Patients, Shana Jacobs

Pediatrics Faculty Publications

Integrative Therapies (IT), otherwise known as Complementary and Alternative Medicine, are widely used among pediatric oncology patients, despite a paucity of available evidence. This review summarizes surveys that describe the prevalence of IT use by pediatric oncology patients, both during therapy and in survivorship, as well as the modalities being used. Additionally, the evidence that exists for specific treatments that appear to be efficacious in controlling specific symptoms is described. Finally, there are recommendations for practitioners on how to best counsel patients about IT use.

Corticosteroids And Pediatric Septic Shock Outcomes: A Risk Stratified Analysis, Sarah J. Atkinson, Natalie Z. Cvijanovich, Neal J. Thomas, Geoffrey L. Allen, Nick Anas, Robert J. Freishtat, +17 Additional Authors

Pediatrics Faculty Publications

Background

The potential benefits of corticosteroids for septic shock may depend on initial mortality risk.

Objective

We determined associations between corticosteroids and outcomes in children with septic shock who were stratified by initial mortality risk.

Methods

We conducted a retrospective analysis of an ongoing, multi-center pediatric septic shock clinical and biological database. Using a validated biomarker-based stratification tool (PERSEVERE), 496 subjects were stratified into three initial mortality risk strata (low, intermediate, and high). Subjects receiving corticosteroids during the initial 7 days of admission (n = 252) were compared to subjects who did not receive corticosteroids (n = 244). Logistic regression …

The Translational Biology Of Remyelination: Past, Present, And Future, Robin J.M. Franklin, Vittorio Gallo

Pediatrics Faculty Publications

Amongst neurological diseases, multiple sclerosis (MS) presents an attractive target for regenerative medicine. This is because the primary pathology, the loss of myelin-forming oligodendrocytes, can be followed by a spontaneous and efficient regenerative process called remyelination. While cell transplantation approaches have been explored as a means of replacing lost oligodendrocytes, more recently therapeutic approaches that target the endogenous regenerative process have been favored. This is in large part due to our increasing understanding of (1) the cell types within the adult brain that are able to generate new oligodendrocytes, (2) the mechanisms and pathways by which this achieved, and (3) …

Vitamin A, Vitamin E, Iron And Zinc Status In A Cohort Of Hiv-Infected Mothers And Their Uninfected Infants, Jacqueline Pontes Monteiro, Maria Leticia Santos Cruz, Marisa Marcia Mussi-Pinhata, Roberta Garcia Salomao, Alceu Jordao Junior, Jennifer S. Read, Jose Henrique Da Silva Pilotto, Rachel Ann Cohen, Sonia Karolina Stoszek, George Kelly Siberry

Pediatrics Faculty Publications

Introduction

We hypothesized that nutritional deficiency would be common in a cohort of postpartum, human immunodeficiency virus (HIV)-infected women and their infants.

Methods

Weight and height, as well as blood concentrations of retinol, α-tocopherol, ferritin, hemoglobin, and zinc, were measured in mothers after delivery and in their infants at birth and at 6-12 weeks and six months of age. Retinol and α-tocopherol levels were quantified by high performance liquid chromatography, and zinc levels were measured by atomic absorption spectrophotometry. The maternal body mass index during pregnancy was adjusted for gestational age (adjBMI).

Results

Among the 97 women 19.6% were underweight. …

Coagulopathy In Newborns With Hypoxic Ischemic Encephalopathy (Hie) Treated With Therapeutic Hypothermia: A Retrospective Case-Control Study, Katie R. Forman, Yaser A. Diab, Edward C.C. Wong, Stephen Baumgart, Naomi L. Luban, An Nguyen Massaro

Pediatrics Faculty Publications

Background

Newborns with hypoxic ischemic encephalopathy (HIE) are at risk for coagulopathy due to systemic oxygen deprivation. Additionally, therapeutic hypothermia (TH) slows enzymatic activity of the coagulation cascade, leading to constitutive prolongation of routinely assessed coagulation studies. The level of laboratory abnormality that predicts bleeding is unclear, leading to varying transfusion therapy practices.

Methods

HIE infants treated with TH between 2008–2012 were included in this retrospective study. Initial, minimum (min) and maximum (max) values of International Normalized Ratio (INR), activated partial thromboplastin time (aPTT), fibrinogen (Fib) and platelet (PLT) count (measured twice daily during TH) were collected. Bleeding was defined …

Neonatal Magnesium Levels Correlate With Motor Outcomes In Premature Infants: A Long-Term Retrospective Cohort Study, Elizabeth Doll, Jacob Wilkes, Lawrence J. Cook, E. Kent Korgenski, Roger G. Faix, Bradley A. Yoder, Rajendu Srivastava, Catherine M.T. Sherwin, Michael G. Spigarelli, Erin A.S. Clark, Joshua L. Bonkowsky

Pediatrics Faculty Publications

OBJECTIVE:

Chronic neurological deficits are a significant complication of preterm birth. Magnesium supplementation has been suggested to have neuroprotective function in the developing brain. Our objective was to determine whether higher neonatal serum magnesium levels were associated with better long-term neurodevelopmental outcomes in very-low birth weight infants.

STUDY DESIGN:

A retrospective cohort of 75 preterm infants (<1500 g, gestational age <27 weeks) had follow-up for the outcomes of abnormal motor exam and for epilepsy. Average total serum magnesium level in the neonate during the period of prematurity was the main independent variable assessed, tested using a Wilcoxon rank-sum test.

RESULTS:

Higher average serum magnesium level was associated with a statistically significant decreased risk for abnormal motor exam (p = 0.037). A lower risk for epilepsy in the group with higher magnesium level did not reach statistical significance (p = 0.06).

CONCLUSION:

This …

Neonatal Nmda Receptor Blockade Disrupts Spike Timing And Glutamatergic Synapses In Fast Spiking Interneurons In A Nmda Receptor Hypofunction Model Of Schizophrenia, Kevin S. Jones, Joshua G. Corbin, Molly M. Huntsman

Pediatrics Faculty Publications

The dysfunction of parvalbumin-positive, fast-spiking interneurons (FSI) is considered a primary contributor to the pathophysiology of schizophrenia (SZ), but deficits in FSI physiology have not been explicitly characterized. We show for the first time, that a widely-employed model of schizophrenia minimizes first spike latency and increases GluN2B-mediated current in neocortical FSIs. The reduction in FSI first-spike latency coincides with reduced expression of the Kv1.1 potassium channel subunit which provides a biophysical explanation for the abnormal spiking behavior. Similarly, the increase in NMDA current coincides with enhanced expression of the GluN2B NMDA receptor subunit, specifically in FSIs. In this study mice …

Tps Mutational Status Is A Potential Marker For Risk Stratification In Wilms Tumour With Diffuse Anaplasia, Mariana Maschietto, Richard D. Williams, Tasnim Chagtai, Sergey D. Popov, Neil J. Sebire, Gordan Vujanic, Elizabeth Perlman, James R. Anderson, Paul Grundy, Jeffrey S. Dome, Kathy Pritchard-Jones

Pediatrics Faculty Publications

Purpose

The presence of diffuse anaplasia in Wilms tumours (DAWT) is associated with TP53 mutations and poor outcome. As patients receive intensified treatment, we sought to identify whetherTP53 mutational status confers additional prognostic information.

Patients and Methods

We studied 40 patients with DAWT with anaplasia in the tissue from which DNA was extracted and analysed for TP53 mutations and 17p loss. The majority of cases were profiled by copy number (n = 32) and gene expression (n = 36) arrays. TP53 mutational status was correlated with patient event-free and overall survival, genomic copy number instability and gene expression profiling. …

Intellectual And Developmental Disability: Healthcare Financing, David A. Ervin, Joav Merrick

Pediatrics Faculty Publications

The World Health Organization (WHO) estimates global spending on healthcare at $6.5 trillion, approximately 10.5% of the world’s gross domestic product. The United States’ (US) share of that spending is $2.6 trillion, essentially quadrupling since 1980. The 2010 United States Patient Protection and Affordable Care Act (PPACA), also known as Obamacare, has stimulated extensive debate over the way in which healthcare is financed, and whether or not the costs of healthcare are sustainable. Among publicly funded healthcare in the US, Medicaid and Medicare are primary sources of funding. In federal fiscal year 2012, Medicaid spending on acute health exceeded $275.4 …

A Delphi Process To Optimize Quality And Performance Of Drug Evaluation In Neonates, Frederic Legrand, Rym Boulkedid, Valery Elie, Stephanie Leroux, Elizabeth Valls, Adolfo Valls-I-Soler, John N. Van Den Anker

Pediatrics Faculty Publications

Background

Neonatal trials remain difficult to conduct for several reasons: in particular the need for study sites to have an existing infrastructure in place, with trained investigators and validated quality procedures to ensure good clinical, laboratory practices and a respect for high ethical standards. The objective of this work was to identify the major criteria considered necessary for selecting neonatal intensive care units that are able to perform drug evaluations competently.

Methodology and Main Findings

This Delphi process was conducted with an international multidisciplinary panel of 25 experts from 13 countries, selected to be part of two committees (a scientific …

Lin28a Expression Reduces Sickling Of Cultured Human Erythrocytes, Jaira F. De Vasconcellos, Ross M. Fasano, Y. Terry Lee, Megha Kaushal, Colleen Burns, Emily Riehm Meier, Molly Anderson, Antoinette Rabel, Raul Braylan, David F. Stroncek, Jeffery L. Miller

Pediatrics Faculty Publications

Induction of fetal hemoglobin (HbF) has therapeutic importance for patients with sickle cell disease (SCD) and the beta-thalassemias. It was recently reported that increased expression of LIN28 proteins or decreased expression of its target let-7 miRNAs enhances HbF levels in cultured primary human erythroblasts from adult healthy donors. Here LIN28A effects were studied further using erythrocytes cultured from peripheral blood progenitor cells of pediatric subjects with SCD. Transgenic expression of LIN28A was accomplished by lentiviral transduction in CD34(+) sickle cells cultivated ex vivo in serum-free medium. LIN28A over-expression (LIN28A-OE) increased HbF, reduced beta (sickle)-globin, and strongly suppressed …

Epidemiology Of Patients Presenting To The Emergency Centre Of Princess Marina Hospital In Gaborone, Botswana, Amit Chandra, Paul C. Mullan, Ari Ho-Foster, Antanoid Langeveldt, Ngaire Caruso, Joseph Motsumi, Andrew Kestler

Pediatrics Faculty Publications

No abstract provided.

Pheochromocytoma In A Twelve-Year-Old Girl With Sdhb-Related Hereditary Paraganglioma-Pheochromocytoma Syndrome, Daryl Graham, Megan Gooch, Zhan Ye, Edward Richer, Aftab S. Chishti, Elizabeth Reilly, John D’Orazio

Pediatrics Faculty Publications

A twelve-year-old girl presented with a history of several weeks of worsening headaches accompanied by flushing and diaphoresis. The discovery of markedly elevated blood pressure and tachycardia led the child's pediatrician to consider the diagnosis of a catecholamine-secreting tumor, and an abdominal CT scan confirmed the presence of a pheochromocytoma. The patient was found to have a mutation in the succinyl dehydrogenase B (SDHB) gene, which is causative for SDHB-related hereditary paraganglioma-pheochromocytoma syndrome. Herein, we describe her presentation and medical management and discuss the clinical implications of SDHB deficiency.

Somatic Intronic Microsatellite Loci Differentiate Glioblastoma From Lower-Grade Gliomas, Enusha Karunasena, Lauren J. Mciver, Brian R. Rood, Xiaowei Wu, Hongxiao Zhu, Jasmin H. Bavarva, Harold R. Garner

Pediatrics Faculty Publications

Genomic studies of glioma sub-types have amassed new disease specific mutations, yet these only partially explain how mutations are linked to predisposition or progression. We hypothesized that microsatellite variation could expand the understanding of glioma etiology. Furthermore, germline markers for gliomas are typically undetectable; therefore we also hypothesize that the predictability of cancer-associated microsatellite loci in germline DNA may support the current hypothesis of a glioma cell of origin.

In this study, “normal” germline exome sequenced DNA from the 1000 Genomes Project (n=390) were compared with exome sequences from germlines of subjects with WHO grade II and III lower-grade glioma …

Newborn Care: What We Can Learn From The Kangaroo Mother, Donald E. Greydanus, Joav Merrick

Pediatrics Faculty Publications

No abstract provided.

Sleep Disturbance, Depression And Pain In Adults With Sickle Cell Disease, Gwenyth R. Wallen, Caterina P. Minniti, Michael Krumlauf, Ellen Eckes, Darlene Allen, Anna Oguhebe, Cassie Seamon, Deepika Darbari

Pediatrics Faculty Publications

Background

Sleep disturbance and depression are commonly encountered in primary care. In sickle cell disease, depression is associated with pain, poor treatment compliance, and lower quality of life. The prevalence of sleep disturbance and its effect upon quality of life in adults with sickle cell disease is unknown. The goal of this study was to determine the prevalence of sleep disturbance and if it is associated with pain and depression in sickle cell disease.

Methods

Three hundred twenty eight adults with sickle cell disease enrolled on the Bethesda Sickle Cell Cohort Study were assessed using the Pittsburgh Sleep Quality Index …

Healthcare For Persons With Intellectual And Developmental Disability In The Community, David A. Ervin, Brian Hennen, Joav Merrick, Mohammed Morad

Pediatrics Faculty Publications

INTRODUCTION: While there has been impressive progress in creating and improving community healthcare delivery systems that support people with intellectual and developmental disabilities (IDD), there is much more that can and should be done.

METHODS: This paper offers a review of healthcare delivery concepts on which new models are being developed, while also establishing an historical context. We review the need for creating fully integrated models of healthcare, and at the same time offer practical considerations that range from specific healthcare delivery system components to the need to expand our approach to training healthcare providers. The models and delivery systems, …

Primary Care: Mental And Behavioral Health And Persons With Intellectual And Developmental Disabilities, David A. Ervin, Ashley Williams, Joav Merrick

Pediatrics Faculty Publications

INTRODUCTION: There are multiple ways to address the mental and behavioral health needs of people with intellectual and developmental disabilities (IDD).

METHOD: In this paper, we do not argue for a particular approach or set of approaches, but instead review the benefits of integrating mental and behavioral health supports with primary healthcare based primarily on our experience in and understanding of healthcare systems in the United States. It is estimated that between 35 and 40% of people with IDD also live with psychiatric disorders. NADD, an association for persons with developmental disabilities and mental health needs in the US holds …

Safety Of Celecoxib And Nonselective Nonsteroidal Anti-Inflammatory Drugs In Juvenile Idiopathic Arthritis: Results Of The Phase 4 Registry, Rachel E. Sobel, Daniel J. Lovell, Hermine I. Brunner, Jennifer E. Weiss, Paula W. Morris, Beth S. Gottlieb, Elizabeth C. Chalom, Lawrence K. Jung, Karen B. Onel, Lisa Petiniot, Donald P. Goldsmith

Pediatrics Faculty Publications

Background

This study aimed to assess long-term safety and developmental data on juvenile idiopathic arthritis (JIA) patients treated in routine clinical practice with celecoxib or nonselective nonsteroidal anti-inflammatory drugs (nsNSAIDs).

Methods

Children aged ≥2 to <18 years with rheumatoid-factor–positive or –negative polyarthritis, persistent or extended oligoarthritis, or systemic arthritis were enrolled into this prospective, observational, multicenter standard-of-care registry. Eligible patients were newly or recently prescribed (≤6 months) an nsNSAID or celecoxib. Enrolled patients were followed to the end of the study, whether they remained on the original NSAID, switched, or discontinued therapy altogether. All adverse events (AEs) regardless of severity were captured in the database.

Results

A total of 274 patients (nsNSAID, n = 219; celecoxib, n = 55) were observed for 410 patient-years of observation. Naproxen, meloxicam, and nabumetone were the most frequently used nsNSAIDs. At baseline, the celecoxib group was older, had a numerically longer median time since diagnosis, and a numerically higher proportion of patients with a history of gastrointestinal-related NSAID intolerance. AEs reported were those frequently …

Controlling Cytomegalovirus: Helping The Immune System Take The Lead, Patrick J. Hanley, Catherine M. Bollard

Pediatrics Faculty Publications

Cytomegalovirus, of the Herpesviridae family, has evolved alongside humans for thousands of years with an intricate balance of latency, immune evasion, and transmission. While upwards of 70% of humans have evidence of CMV infection, the majority of healthy people show little to no clinical symptoms of primary infection and CMV disease is rarely observed during persistent infection in immunocompetent hosts. Despite the fact that the majority of infected individuals are asymptomatic, immunologically, CMV hijacks the immune system by infecting and remaining latent in antigen-presenting cells that occasionally reactivate subclinically and present antigen to T cells, eventually causing the inflation of …

Response To Androgen Therapy In Patients With Dyskeratosis Congenita, Payal P. Khincha, Ingrid M. Wentzensen, Neelam Giri, Blanche P. Alter, Sharon A. Savage

Pediatrics Faculty Publications

Dyskeratosis congenita (DC) is an inherited bone marrow failure syndrome and telomere biology disorder characterized by dysplastic nails, reticular skin pigmentation and oral leucoplakia. Androgens are a standard therapeutic option for bone marrow failure in those patients with DC who are unable to undergo haematopoietic stem cell transplantation, but there are no systematic data on its use in those patients. We evaluated haematological response and side effects of androgen therapy in 16 patients with DC in our observational cohort study. Untreated DC patients served as controls. Seventy percent of treated DC patients had a haematological response with red blood cell …

Pharmacokinetics And Pharmacodynamics Of Antifungals In Children And Their Clinical Implications, Chris Stockmann, Jonathan E. Constance, Jessica K. Roberts, Jared Olson, Elizabeth H. Doby, Krow Ampofo, Justin Stiers, Michael G. Spigarelli, Catherine Mt Sherwin

Pediatrics Faculty Publications

Invasive fungal infections are a significant cause of morbidity and mortality in children. Successful management of these systemic infections requires identification of the causative pathogen, appropriate antifungal selection, and optimisation of its pharmacokinetic and pharmacodynamic properties to maximise its antifungal activity and minimise toxicity and the emergence of resistance. This review highlights salient scientific advancements in paediatric antifungal pharmacotherapies and focuses on pharmacokinetic and pharmacodynamic studies that underpin current clinical decision making. Four classes of drugs are widely used in the treatment of invasive fungal infections in children, including the polyenes, triazoles, pyrimidine analogues and echinocandins. Several lipidic formulations of …

Firesetting And Maltreatment: A Review, Amy L. Burnett, Hatim A. Omar

Pediatrics Faculty Publications

The objective of this review is to determine if a link exists between firesetting offenders and a past history of maltreatment. A literature review was performed using research from various studies and populations. Firesetting is a significant problem that affects the world’s youth today. Even though there is substantial loss of property and life from juvenile firesetters, there is not a great deal of research to provide insight into early identification of those at risk. In the literature review performed, 6 of 7 studies found a link with maltreatment and firesetting behaviors. There does seem to be a correlation between …

Firesetting Behavior And Associated Comorbid Psychiatric Disorders, Stephanie Stockburger, Hatim A. Omar

Pediatrics Faculty Publications

Firesetting behavior results in serious damage to lives and property every year. Firesetting has been linked to a number of comorbid psychiatric disorders including depression, substance abuse, conduct disorder, antisocial personality disorder, obsessive compulsive disorder, psychotic disorder, schizoid personality disorder, and schizophrenia. Psychiatric disorders differ by gender. In addition, juvenile firesetters have history of a separate set of psychiatric comorbidities. The strong correlation between psychiatric comorbidities and firesetting behavior illustrates the need for fire service and mental health collaboration.

Long-Term Consequences Of Childhood Sexual Abuse, Lesley Davidson, Hatim A. Omar

Pediatrics Faculty Publications

The aim of this paper is to summarize the limited studies on post-pubertal consequences of female childhood sexual abuse that includes both psychological distress and physiological stress. The characteristics of sexual abuse are discussed and determined to play a major role in the degree of trauma experienced and in the later effects. The concept of hormones and how disruptions in various endocrine systems can affect the development of these females are examined, especially during the pubertal period. Outcomes of interest included competence, in terms of cognitive, social, self-esteem, and locus of control, and psychopathology including depression, anxiety, dissociation, and hypersexuality. …

Do Not Play With Fire, Joav Merrick, Hatim A. Omar

Pediatrics Faculty Publications

Fire is the rapid oxidation of a material in the exothermic chemical process of combustion, releasing heat, light and various reaction products. Fire is intriguing and therefore something that will attract a curious child from an early age. In 2010, the United States fire department responded to 44,900 fires started by someone, usually a child, playing with fire. These fires caused 90 civilian deaths, 890 civilian injuries and $210 million in direct property damage. Preschoolers and kindergartners are most likely to start these fires, while playing with matches or lighters and most likely to die in these fires. Most fire-play …

Microfluidic-Enabled Liposomes Elucidate Size-Dependent Transdermal Transport, Renee R. Hood, Eric L. Kendall, Mariana Junqueira, Wyatt N. Vreeland, Zenaide M.N. Quezado, Julia C. Finkel, Don L. Devoe

Pediatrics Faculty Publications

Microfluidic synthesis of small and nearly-monodisperse liposomes is used to investigate the size-dependent passive transdermal transport of nanoscale lipid vesicles. While large liposomes with diameters above 105 nm are found to be excluded from deeper skin layers past the stratum corneum, the primary barrier to nanoparticle transport, liposomes with mean diameters between 31–41 nm exhibit significantly enhanced penetration. Furthermore, multicolor fluorescence imaging reveals that the smaller liposomes pass rapidly through the stratum corneum without vesicle rupture. These findings reveal that nanoscale liposomes with well-controlled size and minimal size variance are excellent vehicles for transdermal delivery of functional nanoparticle drugs.

Hospitalization Of Children With Down Syndrome, Ariel Tenenbaum, Rana N. Hanna, Diana Averbuch, Isaiah D. Wexler, Maor Chavkin, Joav Merrick

Pediatrics Faculty Publications

INTRODUCTION: Children with Down syndrome present with multiple medical problems in a higher prevalence compared with the general population, which may lead to hospitalizations.

METHODS: Analysis of 560 hospitalizations of 162 children aged 0-16 years with Down syndrome at Hadassah Medical Center during the years 1988-2007 compared with data on children in the general population, hospitalized at the same period. Data was collected from patient files and statistical data from the Ministry of Health.

RESULTS: Respiratory infections were the leading cause for hospitalization of children with Down syndrome. The number of hospitalizations of children with Down syndrome compared to the …

The Temporal Version Of The Pediatric Sepsis Biomarker Risk Model, Hector R. Wong, Scott L. Weiss, John S. Giuliano Jr., Mark S. Wainwright, Natalie Z. Cvijanovich, Robert J. Freishtat, +19 Additional Authors

Pediatrics Faculty Publications

Background

PERSEVERE is a risk model for estimating mortality probability in pediatric septic shock, using five biomarkers measured within 24 hours of clinical presentation.

Objective

Here, we derive and test a temporal version of PERSEVERE (tPERSEVERE) that considers biomarker values at the first and third day following presentation to estimate the probability of a “complicated course”, defined as persistence of ≥2 organ failures at seven days after meeting criteria for septic shock, or death within 28 days.

Methods

Biomarkers were measured in the derivation cohort (n = 225) using serum samples obtained during days 1 and 3 of septic shock. …